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Kallikrein Protease Involvement in Skin Pathologies Supports a New View of the Origin of Inflamed Itchy Skin

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Proteases and Their Receptors in Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

Skin barrier defects in common dermatological diseases, such as atopic dermatitis and psoriasis, are mostly attributed to anomalies in T-cell immunity. A new viewpoint of inflammatory dermatoses onset was recently suggested, in which barrier defects trigger secretion of pro-inflammatory mediators by stressed keratinocyte cells, which activate the T-cell immune system and further deteriorate the barrier. Herein, we review epidermal keratinocytes as active immune cells. In particular, we focus on recent groundbreaking evidence on the role of keratinocyte-secreted kallikreins as inflammation and allergy mediators. Kallikreins are skin surface proteases known for their role in digesting adhesion proteins and maintaining barrier integrity and function. Kallikrein hyperactivity in skin pathologies was recently shown to mediate inflammation secondary to inherited and acquired barrier defects, in support of the epidermal roots of inflamed and itchy skin. Hence, future therapy design should be directed toward ameliorating keratinocyte-induced barrier defects and inflammation, alone or in combination with dampening T-cell immune responses.

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Acknowledgements

We would like to acknowledge the Natural Sciences and Engineering Council (NSERC) of Canada as our generous funding agency.

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada

    Azza Eissa & Eleftherios P. Diamandis

  2. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Joseph and Wolf Lebovic Centre, 60 Murray Street, Toronto, ON, M5T 3L9, Canada

    Azza Eissa & Eleftherios P. Diamandis

  3. Department of Clinical Biochemistry, University Health Network, Toronto, ON, M5G 1X5, Canada

    Eleftherios P. Diamandis

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  1. Azza Eissa
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Correspondence to Eleftherios P. Diamandis .

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  1. CHU Purpan, INSERM U 563, BP 3028, Toulouse Cedex, 31024, France

    Nathalie Vergnolle

  2. Institut Pasteur, Unite de Defense Innee et Inflammation, INSERM U 874, Rue du Dr. Roux 25, Paris Cedex 15, 75724, France

    Michel Chignard

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Eissa, A., Diamandis, E.P. (2011). Kallikrein Protease Involvement in Skin Pathologies Supports a New View of the Origin of Inflamed Itchy Skin. In: Vergnolle, N., Chignard, M. (eds) Proteases and Their Receptors in Inflammation. Progress in Inflammation Research. Springer, Basel. https://doi.org/10.1007/978-3-0348-0157-7_3

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